Research publication titled: “Isoproterenol-induced heart failure in rat heart: evaluation and cardioprotective strategy.” G. Bourdier, et al. SYNCROSOME. Presented during Printemps de la Cardiologie 2019. Cardiovascular Diseases Supplements Volume 11, Issue 2, April 2019, Page 230
Read the full study here/DOI: https://doi.org/10.1016/j.acvdsp.2019.02.107
Authors:
G. Bourdier, S Robelet,
Affiliations : SYNCROSOME, Luminy biotech entreprises, Marseille, France
Abstract
Introduction
It is well established that cardiac remodelling plays a pivotal role in the development of heart failure (HF), a leading cause of death worldwide. Meanwhile, a preclinical rat model of isoproterenol (Iso)-induced HF causes sympathetic hyperactivity, an important factor of cardiac remodelling, hemodynamic changes and cardiac fibrosis development. Several studies showed that metoprolol, a β1-adrenergic receptor (β1-AR) blocker prevents cardiac dysfunction following prolonged β-AR stimulation in different preclinical models.
Objective
We evaluated the cardioprotective effects of metoprolol on cardiac remodelling and diastolic function in a severe Iso-induced HF model using echocardiography and cardiac pressure measurement.
Method
Rats received Iso injections (Iso; 5 mg/kg/day, N = 5), metoprolol (Meto; 24 mg/kg/day) + Iso 5 (Iso + Meto, N = 6), or vehicle (N = 9) for 7 days. Left ventricular (LV) dimensions and function were followed-up by echocardiography before and after the treatment to assess LV hypertrophy. After echocardiography, LV end-diastolic pressure (LVEDP) was recorded to assess ventricular compliance and rat hearts were used for cardiac remodelling analysis.
Results
One week of Iso injections significantly increased LVEDP (+ 48%) and was associated with a major LV hypertrophy, characterised by a significant increase in LV mass (+ 33%) and a thickening of the LV walls observed by echocardiography. Simultaneous treatment with metoprolol prevented diastolic dysfunction and LV remodelling. Hypertrophy and fibrosis will be analysed in each group by histology (on-going experiments).
Conclusion
Metoprolol afforded a cardioprotective effect on cardiac remodelling and diastolic dysfunction in Iso-induced HF model. Echocardiography and LVEDP measurements validate the reversibility of hypertrophic HF, and Iso-induced HF developed in rat could represent an effective and predictive preclinical model for evaluating antihypertrophic and antifibrotic agents.
